6
B.M. Fraga, I. Cabrera / Tetrahedron xxx (2016) 1e7
(12), 365 (11), 345 (6), 329 (19), 293 (6), 191 (9), 175 (10); [M]þ at
760.3936, C48H56O8 requires 760.3975.
13C NMR: see Table 6; EIMS m/z (rel int.): 760 [M]þ (100), 745 (15),
743 (22), 704 (28), 689 (79), 380 (4), 352 (4); [M]þ at 760.3959,
C48H56O8 requires 760.3975.
3.3. Reaction of precocene I (1) with iron (III) chloride-acetic
acid
3.3.6. Tetramer 17. 1H NMR (500 MHz, CDCl3):
d
1.27, 1.29, 1.38,
1.42, 1.44 and 1.49 (each 3H, s, 6Me), 1.32 (6H, s, 2Me), 1.37 (1H, t,
J¼13.0, H-30), 1.61 (1H, dd, J¼13.0, 5.4 Hz, H-3), 1.70 (1H, dd,
J¼13.0, 5.2 Hz, H-300), 2.04 (1H, dd, J¼13.0, 5.7 Hz, H-30), 2.67 (1H,
t, J¼13.0 Hz, H-300), 2.76 (1H, t, J¼13.0 Hz, H-3), 3.43 (3H, s, OMe0),
3.47 (3H, s, OMe000), 3.70 (1H, dd, J¼1 Hz, dd, J¼13.0, 5.4 Hz, H-4),
3.72 (1H, dd, J¼13.0, 5.2 Hz, H-400), 3.75 (3H, s, OMe00), 3.80 (3H, s,
OMe), 4.41 (1H, dd, J¼13.0, 5.7 Hz, H-40), 5.71 (1H, s, H-3000), 6.25
(1H s, H-80), 6.33 (1H, s, H-8000), 6.39 (1H, s, H-800), 6.42 (1H, s, H-8),
6.43 (1H, s, H-5), 6.53 (1H, s, H-500), 6.87 (1H, s, H-5000), 6.88 (1H, s,
Precocene I (1) (150 mg) in acetic acid (2 ml) was treated with
iron (III) chloride (300 mg) and left with stirring, under nitrogen,
for 4 h at room temperature. Usual work up and chromatography in
silica gel eluting with petroleEtOAc (5%) and HPLC (petroleEtOAc
10%) afforded dimer 5 (8 mg) and tetramers 13 (7 mg), 14 (3 mg), 15
(8 mg), 16 (6 mg), 17 (1.6 mg) and 18 (0.9 mg).
3.3.1. Dimer 5. 1H NMR (500 MHz, CDCl3):
d 1.36 and 1.43 (each 6H,
H-11, H-12), 2.43 (2H, d, 6.3 Hz, H-3), 3.77 (H, s, 2 OMe), 4.75 (2H, d,
J¼6.3 Hz, H-4); 6.36 (2H, d, J¼2.5 Hz, H-8), 6.54 (2H, dd, J¼8.5,
2.5 Hz, H-6), 7.23 (2H, d, J¼8.5 Hz, H-5); 13C NMR: see Table 1; EIMS
m/z (rel int.): 396 [M]þ (46), 381 (6), 343 (13), 336 (14), 308, 274
(23), 245 (66), 229 (15), 206 (25), 191 (90), 175 (88); [M]þ at
396.1935, C24H28O5 requires 396.1936.
H-50); 13C NMR (125 MHz, CDCl3):
d 22.6, 24.8, 25.2, 28.8, 30.3 and
31.8 (6 Me), 27.2 (2 Me), 31.7 (C-40), 32.0 (C-3), 37.3 (C-300), 38.8 (C-
4), 39.1 (C-400), 41.9 (C-30), 55.2 and 55.3 (OMe0, OMe000), 55.4 and
55.7 (OMe, OMe00), 74.8 and 75.0 (C-2, C-200), 75.6 (C-20), 76.0 (C-
2000), 99.2 (C-800), 100.3 (C-8), 101.3 (C-8000), 102.0 (C-80), 112.7 (C-90),
115.2 (C-9000), 116.0 (C-6), 116.2 (C-900), 116.5 (C-9), 121.2 (C-6000),
121.5 (C-60), 123.6 (C-600), 126.6 (C-500), 127.3 (C-4000), 127.8 (C-3000),
129.8 (C-5), 130.5 (C-5000), 133.0 (C-50), 151.8 (C-1000), 152.4 (C-10),
153.7 and 153.8 (C-100, C-10000), 156.3 (C-700), 156.8 (C-7), 157.0 (C-
70), 158.0 (C-7000); EIMS m/z (rel int.): 758 [M]þ (34), 743 (100), 687
(5), 371 (8), 364 (5), 344 (12), 316 (5); [M]þ at 758.3884, C48H54O8
requires 758.3819.
3.3.2. Symmetrical tetramer 13. 1H NMR (500 MHz, CDCl3):
(12H, s, 4H-11), 1.28 (12H, s, 4H-12), 1.65 (4H, t, J¼12.8 Hz, 4H-3
d 1.26
a
),
1.75 (4H, dd, J¼12.8, 5.5 Hz, 4H-3
b
), 3.74 (12H, s, 4OMe), 4.40 (4H,
dd, J¼12.8, 5.5 Hz, 4H-4), 6.10 (4H, s, 4H-5), 6.28 (4H, s, 4H-8); 13
C
NMR: see Table 4; EIMS m/z (rel int.): 760 [M]þ (100), 745 (38), 743
(96), 704 (13), 689 (11), 555 (11), 530 (20), 515 (8), 430 (9), 380 (10),
344 (8), 175 (7); [M]þ at 760.3940, C48H56O8 requires 760.3975.
3.3.7. Tetramer 18. 1H NMR (500 MHz, CDCl3):
d 0.63,1.08,1.11,1.34,
1.39, 1.45, 1.46 and 1.47 (each 3H, s, Me), 1.59 (1H, dd, J¼13.1, 6.2 Hz,
H-30), 1.64 (1H, dd, J¼13.0, 4.2 Hz, H-3000), 1.71 (1H, dd, J¼13.0,
4.3 Hz, H-3), 2.38 (1H, dd, J¼13.0, 2.1 Hz, H-3), 2.51(1H, t, J¼13.0 Hz,
H-3000), 2.60 (1H, t, J¼13.1 Hz, H-30), 3.42 (6H, s, 2 OMe), 3.68 (1H, dd,
J¼13.1, 6.2 Hz, H-40), 3.77 and 3.82 (each 3H, s, OMe), 4.22 (1H, dd,
J¼4.3, 2.1 Hz, H-4), 4.92 (1H, dd, J¼13.0, 4.2 Hz, H-4000), 5.75 (1H, s,
H-300), 6.15 (1H, s, H-5000), 6.25 (1H, s, H-800), 6.34 (1H, s, H-80), 6.35
(1H, d, J¼8.0 Hz, H-6), 6.39 (1H, s, H-50), 6.48 (1H, s, H-8000), 6.83 (1H,
d, J¼8.0 Hz, H-5), 6.95 (1H, s, H-500); 13C NMR (125 MHz, CDCl3), due
to the small amount obtained only some signals could be observed
3.3.3. Symmetrical tetramer 14. 1H NMR (500 MHz, CDCl3):
d 1.25,
1.30, 1.32 and 1.43 (each 6H, s, 2 Me), 1.38 (2H, dd, J¼13.5 and
10.2 Hz, 2H-3), 1.67 (2H, dd, J¼13.0, 5.0 Hz, 2H-30), 2.11 (2H, dd,
J¼13.5, 6.1 Hz, 2H-3), 2.57 (2H, t, J¼13.0 Hz, 2H-30), 3.40 (6H, s, 2
OMe), 3.72 (2H, dd, J¼13.0, 5.0 Hz, 2H-40), 3.82 (6H, s, 2 OMe0), 4.38
(2H, dd, 10.2, 6.1 Hz, 2H-4), 6.22 (2H, s, 2H-8), 6.39 (2H, s, 2H-80),
6.33 (2H, s, H-50), 6.86 (2H, s, H-5); 13C NMR: see Table 4; EIMS m/z
(rel int.): 760 [M]þ (100), 745 (10), 743 (17), 704 (15), 689 (10), 380
(7), 352 (6), 325 (8); [M]þ at 760.3947, C48H56O8 requires 760.3975.
and tentatively assigned: d
28.8 (C-4000), 36.3 (C-4), 37.5 and 37.6 (C-
3.3.4. Tetramer 15. 1H NMR (500 MHz, CDCl3):
d
1.00 and 1.26 (C-
3, C-3000), 38.0 (C-40), 41.8 (C-30), 55.2, 55.5, 55.7 and 56.0 (4 OMe),
99.6, 100.7 and 101.4 (C-80, C-800, C-8000), 105.4 (C-6), 126.1 (C-5),
126.2, 128.6 and 130.0 (C-50, C-500, C-5000), 128.9 (C-400); EIMS m/z (rel
int.): 758 [M]þ (34), 743 (100), 687 (5), 371 (4), 364 (2), 344 (7), 316
(4); [M]þ at 758.3830, C48H54O8 requires 758.3819.
110, C-120), 1.28 and 1.43 (C-11000, C-12000), 1.32 and 1.40 (C-11, C-12),
1.38 and 1.39 (C-1100, C-1200), 1.59 (1H, dd, J¼13.1, 4.4 Hz, H-300), 1.62
(1H, dd, J¼13.6, 6.6 Hz, H-30), 1.65 (1H, t, J¼13.0 Hz, H-3), 1.68 (1H,
dd, J¼13.4, 4.2 Hz, H-3000),1.95 (1H, dd, J¼13.0, 6.5 Hz, H-3), 2.02 (1H,
dd, J¼13.6, 6.6 Hz, H-30), 2.07 (1H, t, J¼13.4 Hz, H-3000), 2.54 (1H, t,
J¼13.1 Hz, H-300), 3.37 (3H, s, OMe0), 3.45 (1H, dd, J¼13.1, 4.4 Hz, H-
400), 3.75, 3.76 and 3.77 (each 3H, s, OMe, OMe00, OMe000), 4.26 (1H, t,
J¼6.6 Hz, H-40), 4.41 (1H, dd, J¼13.4, 4.2 Hz, H-4000), 4.48 (1H, dd,
J¼13.0, 6.5 Hz, H-4), 5.82 (1H, s, H-500), 6.04 (2H, s, H-5, H-5000), 6.10
(1H, s, H-8000), 6.32 (1H, s, H-800), 6.34 and 6.35 (each 1H, s, H-8, H-
80), 6.67 (1H, s, H-50); 13C NMR: see Table 5; EIMS m/z (rel int.): 760
[M]þ (100), 745 (29), 743 (15), 705 (18), 689 (5), 649 (7), 380 (10),
352 (8), 325 (8), 297 (5); [M]þ at 760.3997, C48H56O8 requires
760.3975.
3.4. Reaction of precocene I (1) with iron (III) chloride-acetic
anhydride
To a solution of precocene I (1) (170 mg) in Ac2O (0.84 ml), Fe3Cl
(84 mg) was added and kept with stirring under nitrogen for 1 h at
room temperature. Usual work up and chromatography afforded
encecalin (19) (24 mg).
3.4.1. Encecalin (19). 1H NMR (500 MHz, CDCl3):
d 1.43 (6H, s, H-11,
3.3.5. Tetramer 16. 1H NMR (500 MHz, CDCl3):
d
0.75 and 1.10 (each
H-12), 2.55 (3H, s, eCOeMe), 3.87 (3H, s, OMe), 5.51 (1H, d,
J¼9.8 Hz, H-3), 6.29 (1H, d, J¼9.8 Hz, H-4), 6.37 (1H, s, H-8), 7.52
(1H, s, H-5); 13C NMR: see Table 1; EIMS m/z (rel int.): 232 [M]þ
(46), 217 (100), 174 (4), 144 (3); [M]þ at 232.0959, C14H16O3 requires
232.0947.
3H, s, H-11000, H-12000) 1.08 and 1.25 (each 3H, s, H-11000, H-12000), 1.18
and 1.38 (each 3H, s, H-1100, H-1200), 1.43 and 1.44 (each 3H, s, H-11,
H-12),1.60 (1H, dd, J¼13.0, 6.7 Hz, H-30), 1.61 (1H, dd, J¼13.0, 5.3 Hz,
H-3), 1.72 (1H, dd, J¼13.8, 6.9 Hz, H-300), 1.80 (1H, dd, J¼13.0, 5.5 Hz,
H-3000), 2.12 (1H, dd, J¼13.8, 6.9 Hz, H-300), 2.34 (1H, dd, J¼13.0,
2.5 Hz, H-3), 2.38 (1H, t, J¼13.0 Hz, H-30), 2.44 (1H, t, J¼13.0 Hz, H-
3000), 3.26 (3H, s, OMe), 3.42 (3H, s, OMe00), 3.65 (1H, dd, J¼13.0,
6.7 Hz, H-40), 3.82 (6H, s, OMe0, OMe000), 4.19 (1H, dd, J¼5.3, 2.5 Hz,
H-4), 4.28 (1H, t, J¼6.9 Hz, H-400), 4.89 (1H, dd, J¼13.0, 4.3 Hz, H-4000), s,
H-80), 6.41 (1H, s, H-8000), 6.75 (1H, d, J¼8.3 Hz, H-5), 6.83 (1H, s, H-500);
Acknowledgements
This work has been supported by grant CTQ2015-64049-C3-1-R,
MINECO, Spain.